Regulation of vascular tone by S-nitroso-myoglobin

Abstract

Myoglobin (Mb) is a haem protein present in skeletal, cardiac and smooth muscle where it facilitates the transfer of O2 from the extracellular matrix to the cell cytosol in a cycle termed 'facilitated O2-diffusion'. In addition, we showed recently that recombinant human Mb binds endothelium-derived relaxant factor - nitric oxide (•NO) - via formation of both nitrosyl-haem iron and S-nitroso-myoglobin (S-NO-Mb) [Witting PK, Douglas DJ, Mauk AG. Reaction of human myoglobin and nitric oxide. Heme iron or protein sulfhydryl nitrosation dependence on the absence or presence of oxygen. J Biol Chem 2001; 276: 3991-3998]. S-NO-Mb represents a novel form of endothelium-derived relaxant factor (EDRF) that may be important in maintaining optimal •NO concentrations in the human vasculature. In this study we aim to show that: (i) S-nitrosation of oxygenated ferrous myoglobin (oxyMb) can compete with the rapid oxidation of •NO by oxyMb; and (ii) S-NO-Mb retains characteristics of physiological EDRF. © W. S. Maney & Son Ltd.